scholarly journals The Molecular Basis and Therapeutic Potential of Let-7 MicroRNAs against Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Rei Mizuno ◽  
Kenji Kawada ◽  
Yoshiharu Sakai
Keyword(s):  
Colorectal Cancer ◽  
Molecular Basis ◽  
Posttranscriptional Regulation ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Intestinal Tumorigenesis ◽  
C Elegans ◽  
Microrna Family ◽  
Underlying Mechanisms

Although a number of studies have revealed the underlying mechanisms which regulate the development of colorectal cancer (CRC), we have not completely overcome this disease yet. Accumulating evidence has shown that the posttranscriptional regulation by the noncoding RNAs such as microRNAs plays an important role in the development or progression of CRC. Among a number of microRNAs, the let-7 microRNA family that was first discovered in C. elegans and conserved from worms to humans has been linked with the development of many types of cancers including CRC. The expression level of let-7 microRNAs is temporally low during the normal developmental processes, while elevated in the differentiated tissues. The let-7 microRNAs regulate the cell proliferation, cell cycle, apoptosis, metabolism, and stemness. In CRC, expressions of let-7 microRNAs have been reported to be reduced, and so let-7 microRNAs are considered to be a tumor suppressor. In this review, we discuss the mechanisms regulating the let-7 microRNA expression and the downstream targets of let-7 in the context of intestinal tumorigenesis. The application of let-7 mimics is also highlighted as a novel therapeutic agent.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

scholarly journals Structural and Functional Remodeling of Mitochondria in Cardiac Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4167
Author(s):  
Xiaonan Sun ◽  
Jalen Alford ◽  
Hongyu Qiu
Keyword(s):  
Regulatory Network ◽  
Molecular Basis ◽  
Therapeutic Potential ◽  
Research Direction ◽  
Future Research ◽  
Cardiac Diseases ◽  
Functional Remodeling ◽  
Underlying Mechanisms ◽  
Mitochondrial Remodeling ◽  
Normal Cellular Function

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.

scholarly journals Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

2017 ◽  
Vol 2017 ◽  
pp. 1-38 ◽  
Author(s):  
María Antonia Lizarbe ◽  
Jorge Calle-Espinosa ◽  
Eva Fernández-Lizarbe ◽  
Sara Fernández-Lizarbe ◽  
Miguel Ángel Robles ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Posttranscriptional Regulation ◽  
Genetic Model ◽  
Treatment Options ◽  
Noncoding Rnas ◽  
Developed Countries ◽  
Colorectal Carcinogenesis ◽  
Special Focus ◽  
Epigenetic Alterations ◽  
And Function

Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer.

The Therapeutic Potential of Small Activating RNAs for Colorectal Carcinoma

2019 ◽  
Vol 19 (3) ◽  
pp. 140-146
Author(s):  
Bin Zheng ◽  
QingYun Mai ◽  
JinXing Jiang ◽  
QinQin Zhou
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Gene Activation ◽  
Specific Gene ◽  
Dependent Manner ◽  
Master Regulators ◽  
High Incidence ◽  
Underlying Mechanisms

Small double-strand RNAs have been recognized as master regulators of gene expression. In contrast to the evolutionary conserved RNA interference machinery, which degrades or inhibits the translation of target mRNAs, small activating RNA (saRNA) activates the specific gene in a target dependent manner through a similar mechanism as RNAi. Recently, saRNA mediated expression regulation of specific genes has been extensively studied in cancer researches. Of particular interest is the application of the RNA mediated gene activation within colorectal cancer (CRC) development, due to the high incidence of the CRC. In this review, we summarize the current knowledge of saRNA mediated genetic activation and its underlying mechanisms. Furthermore, we highlight the advantages of the utilization of saRNAs induced gene expression as an investigating tool in colorectal cancer research. Finally, the possibility and the challenge of the saRNA application as a potential therapy for colorectal cancer are addressed.

scholarly journals The developmentally-timed decay of an essential microRNA family is seed sequence-dependent

2021 ◽  
Author(s):  
Bridget Donnelly ◽  
Bing Yang ◽  
Chen-Yu Liu ◽  
Katherine McJunkin
Keyword(s):  
Larval Development ◽  
Therapeutic Potential ◽  
Mirna Family ◽  
Seed Sequence ◽  
Dynamic Regulation ◽  
C Elegans ◽  
Microrna Family ◽  
Necessary And Sufficient ◽  
Mirna Seed ◽  
Mirna Abundance

MicroRNA (miRNA) abundance is tightly controlled by regulation of biogenesis and decay. Here we show that the mir-35 miRNA family undergoes regulated decay at the transition from embryonic to larval development in C. elegans. The seed sequence of the miRNA is necessary and sufficient for this regulation. Sequences outside the seed (3′ end) regulate mir-35 abundance in the embryo but are not necessary for sharp decay at the transition to larval development. Enzymatic modifications of the miRNA 3′ end are neither prevalent nor correlated with changes in decay, suggesting that miRNA 3′ end display is not a core feature of this mechanism and further supporting a seed-driven decay model. Our findings demonstrate that seed sequence-specific decay can selectively and coherently regulate all redundant members of a miRNA seed family, a class of mechanism that has great biological and therapeutic potential for dynamic regulation of a miRNA family′s target repertoire.

From Ocean to Bedside: the Therapeutic Potential of Molluscan Hemocyanins

2018 ◽  
Vol 25 (20) ◽  
pp. 2292-2303 ◽  
Author(s):  
Negar Talaei Zanjani ◽  
Monica Miranda Saksena ◽  
Fariba Dehghani ◽  
Anthony L. Cunningham
Keyword(s):  
Antiviral Activity ◽  
Clinical Efficacy ◽  
Mechanism Of Action ◽  
Therapeutic Agent ◽  
Marine Invertebrates ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Anticancer Properties ◽  
Mechanistic Understanding

Hemocyanins are large and versatile glycoproteins performing various immunological and biological functions in many marine invertebrates including arthropods and molluscs. This review discusses the various pharmacological applications of mollusc hemocyanin such as antiviral activity, immunostimulatory and anticancer properties that have been reported in the literature between the years 2000 and 2016. Emphasis is placed on a better mechanistic understanding of hemocyanin as a therapeutic agent. Elucidation of the mechanism of action is essential to improve the clinical efficacy and for a better understanding of some endogenous immunological functions of this complex glycoprotein.

scholarly journals Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 309
Author(s):  
Lijing Yang ◽  
Mengjia Hu ◽  
Yukai Lu ◽  
Songling Han ◽  
Junping Wang
Keyword(s):  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Inflammasome Activation ◽  
Hematopoietic Stem ◽  
Hematopoietic Transplantation ◽  
Proliferation And Differentiation ◽  
Extracellular Stimuli ◽  
Transplantation Complications ◽  
Underlying Mechanisms

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

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